General and emotion-specific neural effects of ketamine during emotional memory formation

Abstract

General and emotion-specific neural effects of ketamine during emotional memory formation, NeuroImage, http://dx.doi.org/10. 1016/j.neuroimage.2017.02.049 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractAnimal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dependent signalling in limbic and prefrontal regions is critically involved in both cognitive and emotional functions. In humans, ketamine-induced transient, and disorder associated chronic NMDAR hypofunction (i.e. in schizophrenia) has been associated with deficient performance in the domains of memory and higher-order emotional functioning, as well as altered neural activity in the underlying limbicprefrontal circuits. To model the effects of NMDAR hypofunction on the integration of emotion and cognition the present pharmacological fMRI study applied the NMDAR antagonist ketamine (target plasma level = 100ng/ml) to 21 healthy volunteers in a within-subject placebo-controlled crossover 2 design during encoding of neutral, positive and negative pictures. Our results show that irrespective of emotion, ketamine suppressed parahippocampal and medial prefrontal activity. In contrast, ketamine selectively increased amygdala and orbitofrontal activity during successful encoding of negative stimuli. On the network level ketamine generally increased medial prefrontalparahippocampal coupling while specifically decreasing amygdala-orbitofrontal interplay during encoding of negative stimuli. On the behavioural level, ketamine produced generally decreased memory performance and abolished the emotional enhancement of memory after a wash-out period of 5 days. The present findings suggest that ketamine produces general as well as valencespecific effects during emotional memory formation. The pattern partly overlaps with alterations previously observed in patients with schizophrenia.

Medial prefrontal activity at encoding determines enhanced recognition of threatening faces after 1.5 years

“…The consistent results with those found in univariate analysis not only illustrate the potential of data-driven multivariate methods for analyzing On the other hand, the small number of face images for each expression condition and the low hits did not permit a trial-wise fMRI analysis comparing remembered versus non-remembered items as in the majority of previous studies examining emotional memory effects (e.g. Becker et al, 2017). Future studies using a larger set of face stimuli of each expression are needed to further explore the subsequent memory effect of emotion.…”

“…On the other hand, the small number of face images and the low number of hits for each expression condition did not permit a sufficiently powered trial-wise fMRI analysis comparing remembered versus non-remembered items as in the majority of previous studies examining emotional memory effects (e.g. Becker et al, 2017; Dolcos et al, 2005). Future studies using a larger set of face stimuli of each expression are needed to further explore the subsequent memory effect of emotional expression.…”

Glutamatergic Deficits in Schizophrenia – Biomarkers and Pharmacological Interventions within the Ketamine Model

“…Becker et al [ 86 ] investigated ketamine effects on the encoding of negative, neutral and positive images in a randomized, double-blind, placebo-controlled study. Regardless of the emotional content of stimuli ketamine decreased the activation of the right para-hippocampal gyrus and the mPFC during encoding.…”

“…Functional connectivity between left amygdala and the ipsilateral frontal orbital cortex was reduced during encoding of negative stimuli. On the other hand, coupling between the left mPFC and right hippocampus was increased irrespective of the emotional content [ 86 ]. Scheidegger et al [ 87 ] investigated ketamine effects under emotional stimulation compared to baseline.…”

Alcohol and pharmacologically similar sedatives impair encoding and facilitate consolidation of both recollection and familiarity in episodic memory

“…It is worth noting, however, that every study in Table 1 implemented minimal delays between encoding and retrieval, thereby opening up the possibility that the GABA A PAM manipulations also impacted memory retrieval. When drug effects have been isolated to either encoding or retrieval by implementing delays between these phases, encoding manipulations modulate hit rates (e.g., Ballard, Gallo, & de Wit, 2013; Becker et al, 2017; Weafer et al, 2016a), whereas retrieval manipulations increase false alarm rates (Ballard, Gallo, & de Wit, 2014; Doss, Weafer, Gallo, & de Wit, 2018a, 2018b). Indeed, increases in false alarm rates were observed in the drug conditions of some of the studies in Table 1.…”